Sodium Carbonate → methyl 3-cyclohexyl-2-(4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)-1H-indole-6-carboxylate

HRID 1518249ノート

反応式

HRID 1518249 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:10](Br)[NH:11]2)=[CH:7][CH:6]=1)=[O:4].N1C2C(=CC=C(C(OC)=O)C=2)C=C1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[C:38]([CH2:45][O:46][Si:47]([CH:54]([CH3:56])[CH3:55])([CH:51]([CH3:53])[CH3:52])[CH:48]([CH3:50])[CH3:49])[CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:15]1([C:9]2[C:8]3[C:12](=[CH:13][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)[NH:11][C:10]=2[C:39]2[CH:40]=[CH:41][C:36]([O:35][CH3:34])=[CH:37][C:38]=2[CH2:45][O:46][Si:47]([CH:48]([CH3:50])[CH3:49])([CH:54]([CH3:56])[CH3:55])[CH:51]([CH3:53])[CH3:52])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 639844Methyl indole-6-carboxylateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylateHCID 67345879(4-Methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)boronic acid

生成物 1

HCID 67345419methyl 3-cyclohexyl-2-(4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)-1H-indole-6-carboxylate収率 81%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

2-Bromo-3-cyclohexyl indole-6-carboxylic acid methyl ester (1 eq., prepared as described in WO2004/087714 from commercially available methyl indole-6-carboxylate) and (4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)boronic acid (1.1 eq.) were dissolved in dioxane (0.125M solution) and 2M aq. sodium carbonate solution (3.3 eq.) was added. The mixture was degassed and flushed with argon. Then bis(triphenylphosphine)palladium dichloride (0.1 eq.) was added and the mixture was heated under argon atmosphere to 110° C. After 5 h at this temperature all volatiles were evaporated in vacuo and the residual material was dissolved in EtOAc. The solution was extracted with water and with brine, then dried over Na2SO4 and evaporated in vacuo. The residual material was purified by flash chromatography (PE:EtOAc, 9:1). After evaporation of the solvents the product was obtained as an off-white foam (81%). The material was used without further characterization in the next reaction.

後処理

  1. customThe mixture was degassed
  2. customflushed with argon
  3. customAfter 5 h at this temperature all volatiles were evaporated in vacuo
  4. dissolutionthe residual material was dissolved in EtOAc
  5. extractionThe solution was extracted with water and with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customThe residual material was purified by flash chromatography (PE:EtOAc, 9:1)
  9. customAfter evaporation of the solvents the product

出典と根拠

ORDレコード
ord-a0ff40f2092d4578a79c76efb0bfe385
出典データセット
uspto-grants-2012_07
特許番号
US08232390B2

反応ノート

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